Abstract Introduction The RAVE/RITUXIVAS trials established rituximab (RTX) therapy in ANCA-associated vasculitis (AAV). However, RAVE excluded patients with severe renal involvement (creatinine > 354 µmol/L). Whilst RITUXIVAS did not, treatment included RTX with 2 cyclophosphamide (CYC) pulses. This study reports outcomes in AAV patients with severe renal involvement treated with RTX alone compared to CYC, together with high dose steroids. Methods Data were collected retrospectively for all consecutive AAV presentations with severe renal involvement (peak creatinine >354 µmol/L) between 2010–2023 from two renal units. The primary outcome was sustained remission with independent renal function at 12 months. Results Amongst 107 de novo AAV patients, 66 received pulsed CYC with steroids (39 received plasma exchange (PLEX)), and 41 received RTX with steroids (7 received PLEX). At presentation, there was no significant difference in, renal replacement therapy requirement (CYC, 56% vs RTX, 71%; p = 0.129), peak creatinine (511 vs 538 µmol/L; p = 0.399) or eGFR (9 vs 7 mL/min/1.73m2; p = 0.372). 52% of CYC patients, and 49% of RTX patients met the primary outcome (p = 0.783). At 12 months, there was no significant difference in the proportion of patients with independent renal function (CYC, 65% vs RTX, 56%; p = 0.582), eGFR was similar between CYC and RTX patients (28 vs 31 mL/min/1.73m2, p = 0.439), and 94% of CYC cohort were alive compared to 83% of RTX (p = 0.068). Conclusion RTX with steroids is comparable to CYC with steroids to successfully induce remission in AAV with severe renal involvement.
Nephrotic syndrome (NS) encompasses a heterogeneous group of glomerular diseases characterized by heavy proteinuria, hypoalbuminemia, edema, and multiple systemic complications. Despite substantial advances in diagnostic techniques and targeted therapies, the management of NS remains challenging in clinical practice. In addition to complex treatment decisions, clinicians must address diagnostic uncertainty, recognize secondary causes, and prevent potentially serious complications including thrombosis, infections, cardiovascular disease, and progressive kidney dysfunction. Adverse outcomes in NS frequently arise not only from inappropriate management but also from overlooked steps in diagnosis, monitoring, and long-term care. Here, we present 10 practical tips to improve clinical decision-making in the diagnosis and management of NS. Key positive strategies include appropriate use of kidney biopsy and modern immunopathologic techniques, integration of immunologic biomarkers such as anti-phospholipase A2 receptor antibodies in the evaluation of membranous nephropathy, systematic exclusion of secondary causes, and comprehensive supportive care including blood pressure control, antiproteinuric therapy, and thrombosis prophylaxis in high-risk patients. In addition, evidence-based use of immunosuppressive therapies (IST) tailored to specific disease entities is emphasized. Equally important are commonly overlooked pitfalls that may compromise outcomes, including delayed genetic testing in steroid-resistant disease, prolonged ineffective immunosuppression, inadequate post-transplant surveillance for recurrence, under-recognition of cardiovascular risk, and failure to prevent complications associated with IST. Highlighting these practical considerations may help increase awareness of common pitfalls and support more attentive clinical management of patients with NS.
The start of hemodialysis is a particularly vulnerable phase in a patient's journey through various stages of kidney disease: Early mortality is high, functional decline is common, and many patients feel poorly informed and unprepared for what dialysis entails. Decisions made during this phase shape long-term trajectories. Here, we aim at providing "suggestions for colleagues" rather than guideline-like recommendations. In our six tips regarding dialysis consent, transplant candidacy, pill check, vaccination, exercise, and nutrition, we cover the direct patient-doctor axis. In our four tips on volume management, modality, anticoagulation, and incremental hemodialysis, we provide advice that may benefit patients through the prescription itself. Our choice of items is incomplete, as important aspects like vascular access, anemia management, mineral bone disorder, patient-reported symptoms, and dialysate composition are missing. Altogether, we hope that our contribution can emphasize, that hemodialysis may be viewed as the cradle rather than the dead end of nephrology, and enthusiasm for the accomplishments of hemodialysis over the years can ultimately outperform frustration over the burden it imposes on patients. Today's many options to modify hemodialysis for the better represent professional challenges, but these can ultimately be used, right from the start, such as to build the perfect, individualized patient package that should be hemodialysis treatment today.
The use of recombinant human granulocyte-colony stimulating factor (G-CSF) is an uncommon aetiology for acute kidney injury in cancer patients. Several patterns of renal injury due to G-CSF have been discussed in the literature. Here, we present a case of a 48-year-old man with monoclonal gammopathy of renal significance who received filgrastim for planned autologous stem cell transplantation and developed acute kidney injury presenting as crescentic glomerulonephritis. The patient was treated with steroids, plasmapheresis, and cyclophosphamide. He attained complete recovery and proceeded with stem cell transplantation. We conducted an extensive review of the literature on the subject, which revealed that 10 of the 18 biopsy-proven cases of G-CSF-induced renal injury presented as crescentic glomerulonephritis. When G-CSF is administered to patients with an underlying renal pathology (usually autoimmune or monoclonal in aetiology), the migration and degranulation of activated neutrophils in the glomerular microenvironment in large numbers results in glomerular basement membrane rupture and crescent formation. Timely renal biopsy and aggressive initiation of treatment aid in attaining renal recovery and a favourable prognosis in cancer patients.
Abstract Background Renin-angiotensin system (RAS) inhibitors are a cornerstone of cardiovascular and kidney risk modification in chronic kidney disease (CKD). Yet, they are often discontinued in advanced CKD to limit adverse effects or to delay kidney replacement therapy (KRT). Methods From the CKD-Renal Epidemiology and Information Network prospective cohort study, we selected participants with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 and treated with RAS inhibitors. We performed a target trial emulation with parametric g-formula to compare two strategies: to discontinue or to continue RAS inhibitors. Models were adjusted for sociodemographics, clinical and laboratory characteristics, and drug prescriptions. Outcomes were the composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, i.e. major cardiovascular events (MACE), and KRT initiation. Results Among the 1 434 patients included (median age 68 years, median eGFR 25 mL/min/1.73m2, 35% women), 386 (27%) discontinued RAS inhibitors over a median follow-up of 35 months. Very few events related to adverse drug reactions were reported in the 3 months preceding RAS inhibitor discontinuation (n = 23), but their incidence over this period was ∼13-fold higher than that during the entire follow-up. The 3-year adjusted relative risk of MACE associated to discontinuing RAS inhibitors, compared to continuing, was 2.02 (95% CI, 1.62 to 2.47), and that of KRT initiation, 1.34 (95% CI, 1.14 to 1.60). Discussion RAS inhibitor discontinuation was strongly associated with MACE and KRT risks, major causes of morbidity and mortality in advanced CKD. Our findings, consistent with prior data, suggest the risk-benefit balance favors continued use with close monitoring.
Abstract Background APOL1 risk variants are strongly associated with kidney disease in individuals of recent African ancestry, but their haemodynamic effects remain incompletely characterised, particularly in African dialysis populations. We evaluated the association between APOL1 variants and blood pressure phenotypes in a South African haemodialysis cohort. Methods In this cross-sectional study, 115 adults receiving maintenance haemodialysis in Pretoria were included. All participants were self-identified Black Africans. APOL1 genotyping (G1: rs73885319, rs60910145; G2: rs71785313) was performed, and genetic models were analysed as additive, dominant, and recessive. Pre-dialysis blood pressure was defined as the mean of five consecutive measurements. Outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP). Associations were assessed using linear mixed-effects models with dialysis site as a random effect, with sequential adjustment for age, sex, and antihypertensive class burden. Results APOL1 risk allele distribution was 53.0% zero, 36.5% one, and 10.4% two alleles. There were no consistent associations between APOL1 genotype and SBP, DBP, or MAP in univariate analyses. In multivariable models, SBP was significantly lower in APOL1 risk allele carriers under additive and dominant models. In contrast, PP was consistently lower in APOL1 risk allele carriers and remained significant after full adjustment (additive model, one vs zero: β -7.772, 95% CI -13.009 to -2.535, P = 0.004; dominant model: β -7.69 95% CI -12.622 to -2.757, P = 0.003). No consistent associations were observed for DBP or MAP. Conclusions In this cohort of Black African haemodialysis patients, APOL1 risk variants were associated with lower PP and, after adjustment, lower SBP, without differences in DBP or MAP. These findings suggest a distinct haemodynamic phenotype characterised by reduced arterial pulsatility and highlight the need for further mechanistic and prospective studies, particularly in the context of emerging APOL1-targeted therapies.
Abstract Systemic lupus erythematosus (SLE) is associated with significant cardiovascular morbidity, with myocardial involvement representing one of the most clinically significant yet underrecognized cardiac manifestations, largely due to its frequently subclinical presentation and diagnostic complexity. Lupus nephritis (LN), a common and clinically significant manifestation of SLE, is further associated with increased cardiovascular risk, reflecting a dynamic cardiorenal interaction driven by persistent immune activation. Recent advances in cardiovascular imaging techniques have facilitated the early detection of myocardial injury in SLE, improving diagnostic accuracy and enabling timely intervention, but have also uncovered the increased possibility of subclinical, underdiagnosed cases. Herein, this review focuses on myocardial disease in SLE, outlining the diagnostic tools available for early detection of myocardial complications.
Abstract Depression is relatively common in patients with kidney failure treated with hemodialysis, and the prevalence rate exceeds that of the general population. Depression should be treated in people maintained on dialysis, both due to depression’s inherent significance and its potential complications for kidney treatment. This paper reviews the relevant literature on reported pharmacological and non-pharmacological approaches. Although the evidence base is somewhat limited, recent clinical trials have allowed formulation of practical treatment recommendations. The literature on pediatric CKD is also reviewed. Although the evidence base is scarce, treatment recommendations for the pediatric population are discussed. Various barriers to the integration of standardized depression screening and treatment for people with kidney failure treated with hemodialysis are reviewed.
Abstract Background Heterozygous pathogenic variants in COL4A3 or COL4A4 are relatively common and associated with a broad clinical spectrum. However, nomenclature and risk stratification remain unsettled. We aimed to investigate temporal diagnostic trends and clinical features of haematuria-positive individuals with heterozygous COL4A3/COL4A4 variants in a genetic testing cohort. Methods This retrospective cohort study involved 992 families genetically diagnosed with Alport syndrome at a single centre in Japan between 2006 and 2023. We identified 265 families comprising 299 haematuria-positive individuals with heterozygous pathogenic or likely pathogenic COL4A3/COL4A4 variants. For kidney failure (KF) analysis, 627 individuals, including affected relatives, were evaluated. Results At the family level, the proportion of the study group increased from 8.4% of genetically diagnosed Alport syndrome cases during the Sanger sequencing era (2006–2015) to 26.6% during early next-generation sequencing implementation (2015–2019), and 39.1% in the recent period (2020–2023). At genetic diagnosis, 75.3% of individuals had proteinuria and 4.7% had KF. Kaplan–Meier analysis showed that the median ages at first detection of haematuria and proteinuria, and at onset of KF, were 10, 26, and 72 years, respectively. Conclusions Individuals with haematuria and heterozygous COL4A3/COL4A4 variants accounted for an increasing proportion of genetically diagnosed cases of Alport syndrome. Although this referred cohort does not represent all individuals with heterozygous COL4A3/COL4A4 variants, our findings delineate the natural history of haematuria-positive individuals with these variants and may support early diagnosis and risk stratification aimed at preventing progression to KF.
Trajectory analysis investigates patterns of change over time of variables across various fields, including clinical and public health research. This method is useful for understanding the evolution of behaviors, conditions, and biomarkers (such as serum creatinine, blood pressure, etc.) over time. In medicine, by examining trajectories, researchers can identify distinct clinical patterns and assess the impact of risk factors and interventions on these patterns. This paper explores some theoretical and practical aspects of trajectories analysis by focusing on group-based trajectory models (GBTM) and emphasizing the importance of this approach in clinical research by providing guidance on its implementation using STATA software.
Introduction:Patients with myocardial infarction (MI) or heart failure (HF) often have concomitant chronic kidney disease (CKD). These patients are perceived as 'complex', but empirical evidence quantifying this complexity or exploring the diseases and problems they experience is scarce. We aimed here to comprehensively characterize the complexity of care among patients with MI/HF across the spectrum of CKD severity and to identify frequent longitudinal disease accrual trajectories associated with all-cause mortality. Methods:Retrospective cohort of 29 901 adults surviving an incident MI/HF hospitalization from the Stockholm CREAtinine Measurements (SCREAM, 2006-2021) project. KDIGO CKD stages were classified as no CKD, mild CKD, or moderate-to-severe CKD using plasma creatinine and urinary albumin at hospital admission. Care complexity was evaluated through multidimensional indicators encompassing comorbid conditions, treatments, healthcare use, and mortality. Process mining identified longitudinal trajectories of disease accrual and associated mortality risks. Results:Increasing CKD severity was associated with greater comorbidities, polypharmacy, healthcare use, and higher observed rate of recurrent MI/HF and death. We identified 8927 hospitalizations and 20 805 outpatient disease trajectories during follow-up. CKD patients more often accumulated multiple circulatory diagnoses, significantly increasing mortality hazards compared with those without CKD. Trajectories involving progression to endocrine/metabolic, respiratory, neoplastic, and genitourinary diseases became more frequent with advancing CKD and were strongly associated with death. Conclusions:Among MI/HF survivors, those with CKD are the most complex and resource-demanding. We identified key comorbidity patterns that provide opportunities for earlier, targeted interventions-particularly addressing endocrine, respiratory, and neoplastic complications-to reduce their adverse outcomes and premature mortality.
Translating the 2024 KDIGO (Kidney Disease: Improving Global Outcomes) lupus nephritis (LN) guideline update into routine care remains challenging. While clinical trial data support early multi-agent combination therapy for nephritis to optimize kidney protection, real-world implementation is constrained by disease heterogeneity, disparities in access to advanced therapeutics, and limited incorporation of cost-effectiveness considerations. In this perspective article, we propose a pragmatic framework to adapt KDIGO recommendations to diverse healthcare settings. First, we propose a stratification model integrating clinical response kinetics, serological markers, and histological chronicity. Second, we apply implementation science frameworks to identify diagnostic and therapeutic gaps. Finally, we outline a value-based approach to evaluate the use of biologics and small molecules in terms of short- and long-term clinical outcomes and economic sustainability. Together, these strategies provide a roadmap to improve the real-world applicability of modern LN management.
Background:Renal sarcoidosis is a rare manifestation of systemic sarcoidosis. Evidence guiding management remains limited. We aimed to characterize clinical and histopathological features, renal outcomes, and predictors of recovery and relapse in patients with renal sarcoidosis. Methods:In this retrospective, multicenter observational study across hospitals affiliated with the Spanish Group for the Study of Glomerular Diseases, we included patients with biopsy-confirmed renal sarcoidosis and ≥6 months of follow-up. Primary outcomes were renal recovery (defined as >50% improvement in estimated glomerular filtration rate) and disease relapse (renal or extrarenal). Secondary outcomes included progression to end-stage kidney disease (ESKD) and treatment-related complications. Results:In this study, 60 patients with a mean age of 56.8 years were included. Tubulointerstitial involvement predominated (80%), with granulomatous interstitial nephritis in 56.7%, while 23.3% exhibited glomerular disease. Patients with interstitial-only patterns achieved more frequently renal recovery at 12 months compared with those with glomerular involvement (65.9% vs 20%, P = .013). Intravenous corticosteroid pulses were associated with faster renal improvement in our cohort, although it should be interpreted cautiously because of potential indication bias. Higher oral corticosteroid doses, prolonged high-dose exposure, or slower tapering strategies did not improve renal outcomes and were associated with increased complications. Over a median follow-up of 36 months, 38.3% of patients experienced relapse, and 6.7% of patients progressed to ESKD. Conclusions:Renal sarcoidosis exhibits heterogeneous presentations but substantial potential for renal recovery, particularly in patients with granulomatous interstitial nephritis. These findings may support further investigation of pathology-informed treatment strategies aimed at reducing corticosteroid exposure. Prospective studies are needed to define optimal treatment strategies.
Background and hypothesis:Accurate assessment of glomerular filtration rate (GFR) is essential during evaluation of prospective kidney donors. While estimated GFR (eGFR) equations are widely used in clinical practice, evidence regarding their performance in individuals with preserved renal function remains limited. We evaluated the agreement of creatinine, cystatin-C, and combined biomarker eGFR equations against measured GFR (mGFR) calculated using iohexol plasma clearance in healthy prospective kidney donors. Methods:We conducted a retrospective observational study of adults undergoing kidney donor assessment at a tertiary UK centre between 2015 and 2018. Serum creatinine and cystatin-C were compared with iohexol plasma clearance. Ten validated eGFR equations were evaluated. Agreement was assessed using Lin's concordance correlation coefficient, bias, P10, P30, and Bland-Altman analyses. Sensitivity and specificity were calculated for each eGFR equation against British Transplant Society age- and sex-specific mGFR donor suitability thresholds. Results:One hundred seven participants were included; 50.5% were females, mean age was 48.5 ± 11.8 years and mean mGFR was 86.5 ± 14.6 ml/min/1.73 m2. The Lund-Malmo revised equation (LMR) had the most favourable agreement metrics, followed by European Kidney Function Consortium (EKFC). LMR had the highest correlation coefficient (r = 0.70; 95% confidence intervals (CI): 0.58 to 0.78), smallest bias (-1.3 ± 10.9 ml/min/1.73 m2), highest P30 (97.2%; 95% CI: 94.1-100), and highest P10 (57.0%; 95% CI 47.6-66.4). P30 exceeded 80% across most equations, whereas P10 was lower, ranging from 29.0% to 57.0%. Sensitivity for identifying donor suitability thresholds was generally high, ranging from 75.6% to 98.7%, whereas specificity was lower, ranging from 17.2% to 58.6%. Conclusions:In healthy kidney donors with preserved kidney function, creatinine-based equations, particularly LMR and EKFC, demonstrated improved agreement with iohexol plasma clearance than cystatin-C-based approaches. Despite acceptable population-level performance, low P10 and substantial variability support continued use of mGFR during evaluation of prospective kidney donors.
Abstract Background The disease spectrum of intratubular light chain amyloidosis (AL) remains unkown. Methods Patients with intratubular AL from a single center were retrospectively analyzed and stratified into 3 groups: Group 1, complicated by extra-tubular amyloidosis; Group 2, complicated by light chain cast nephropathy (LCCN); and Group 3, isolated intratubular AL. Clinical features, pathological findings, treatment regimens, and renal prognosis were compared across the groups. Results The cohort (126 patients) was predominantly male (65.1%), with a mean age of 57 years and a high prevalence of the λ-light chain (78.6%). Group 1 was characterized by the lowest serum creatinine (Scr) and albumin, but the highest urinary protein and prevalence of systemic amyloidosis (all P < 0.05). Group 2 presented with higher Scr, prevalence of anemia and multiple myeloma (MM), elevated involved-to-uninvolved light chain ratio, and increased density of amyloid casts compared with Group 1 (all P < 0.05). Group 3 displayed similar hematological parameters and amyloid cast density as Group 1, with 1 patient displaying extrarenal amyloidosis. Overall, the hematological response rate was 54.3% and the renal remission rate was 26.4%. One patient in Group 3 progressed to MM. Group 2 had the highest incidence of end-stage renal disease (P < 0.05). Multivariate analysis identified Scr at biopsy as an independent predictor of renal prognosis. Conclusion Intratubular AL is frequently identified in patients with renal AL and LCCN, presenting with characteristics associated with these two disorders. Isolated intratubular AL could progress to MM or systemic amyloidosis, thereby necessitating vigilant clinical monitoring.
